Random X-chromosome inactivation dynamics in vivo by single-cell RNA sequencing.
Random X-chromosome inactivation dynamics in vivo by single-cell RNA sequencing.
复制标题
通过单细胞 RNA 测序研究体内随机 X 染色体失活动力学
DOI：
10.1186/s12864-016-3466-8
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发表时间：
2017-01-17
期刊：
影响因子：
4.4
通讯作者：
Liu L
中科院分区：
文献类型：
--
作者：
Wang M;Lin F;Xing K;Liu L
随机X染色体失活（rXCI）对于维持雌性真兽目哺乳动物正常的体细胞功能非常重要。X染色体失活起始的动力学已经通过评估胚胎干细胞体外分化而被广泛研究。为了研究体内的现象，我们应用RNA测序从两个遗传上遥远的小鼠品系的自然杂交获得的雌性胚胎的单细胞。本研究中的非活性X染色体不是人工指定非活性X染色体的亲本来源，而是从自然发育时期随机选择的，因此包括父本和母本来源。来自同一发育阶段的单个细胞的rXCI阶段表现出异质性。显示了rXCI动力学的高分辨率。X染色体基因的失活顺序由它们的功能、表达水平和位置决定;一般来说，失活顺序不表现出亲本来源偏好。发现了新的逃逸基因。Ohno的剂量补偿假说被我们的植入后阶段数据所反驳。我们发现X染色体基因的失活顺序是由其自身的性质决定的。一般来说，失活顺序没有表现出父母的起源偏好。它提供了对体内rXCI期间基因沉默动态的见解。本文的在线版本（doi：10.1186/s12864-016-3466-8）包含补充材料，可供授权用户使用。
Random X-chromosome inactivation (rXCI) is important for the maintenance of normal somatic cell functions in female eutherian mammals. The dynamics of X-chromosome inactivation initiation has been widely studied by assessing embryonic stem cell differentiation in vitro. To investigate the phenomenon in vivo, we applied RNA sequencing to single cells from female embryos obtained from a natural intercrossing of two genetically distant mouse strains. Instead of artificially assigning the parental origin of the inactive X chromosome, the inactive X chromosomes in this study were randomly selected from the natural developmental periods and thus included both paternal and maternal origins. The rXCI stages of single cells from the same developmental stage showed heterogeneity. The high resolution of the rXCI dynamics was exhibited. The inactivation orders of X chromosomal genes were determined by their functions, expression levels, and locations; generally, the inactivation order did not exhibit a parental origin preference. New escape genes were identified. Ohno’s hypothesis of dosage compensation was refuted by our post-implantation stage data. We found the inactivation orders of X chromosomal genes were determined by their own properties. Generally, the inactivation order did not exhibit a parental origin preference. It provided insights into the gene silencing dynamics during rXCI in vivo. The online version of this article (doi:10.1186/s12864-016-3466-8) contains supplementary material, which is available to authorized users.